title: Overexpression of membrane proteins in primary and metastatic gastrointestinal neuroendocrine tumors.
abstract: BACKGROUND
  Small bowel and pancreatic neuroendocrine tumors (SBNETs and PNETs) are rare tumors whose incidence is increasing. Drugs targeting the somatostatin receptor are beneficial in these tumors. To identify additional cell-surface targets, we recently found receptors and membrane proteins with gene expression significantly different from adjacent normal tissues in a small number of primary SBNETs and PNETs. We set out to validate these expression differences in a large group of primary neuroendocrine tumors and to determine whether they are present in corresponding liver and lymph node metastases.
  
  
  METHODS
  Primary SBNETs and PNETs, normal tissue, nodal, and liver metastases were collected and mRNA expression of six target genes was determined by quantitative PCR. Expression was normalized to GAPDH and POLR2A internal controls, and differences as compared to normal tissue were assessed by Welch's t test.
  
  
  RESULTS
  Gene expression was determined in 45 primary PNETs with 20 nodal and 17 liver metastases, and 51 SBNETs with 50 nodal and 29 liver metastases. Compared to normal tissue, the oxytocin receptor (OXTR) showed significant overexpression in both primary and metastatic SBNETs and PNETs. Significant overexpression was observed for MUC13 and MEP1B in PNET primary tumors, and for GPR113 in primary SBNETs and their metastases. SCTR and ADORA1 were significantly underexpressed in PNETs and their metastases. OXTR protein expression was confirmed by immunohistochemistry.
  
  
  CONCLUSIONS
  OXTR is significantly overexpressed relative to normal tissue in primary SBNETs and PNETs, and this overexpression is present in their liver and lymph node metastases, making OXTR a promising target for imaging and therapeutic interventions.
authors.affiliation: Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Carr
authors.affiliation: Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA.
authors.forename: Scott K
authors.initials: SK
authors.lastname: Sherman
authors.affiliation: Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA.
authors.forename: Donghong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA.
authors.forename: Fadi S
authors.initials: FS
authors.lastname: Dahdaleh
authors.affiliation: Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, IA.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Bellizzi
authors.affiliation: Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA.
authors.forename: M Sue
authors.initials: MS
authors.lastname: O'Dorisio
authors.affiliation: Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: O'Dorisio
authors.affiliation: Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA.
authors.forename: James R
authors.initials: JR
authors.lastname: Howe
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D005770:Gastrointestinal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D007421:Intestine, Small / Q000378:metabolism* / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D008207:Lymphatic Metastasis; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism; D009077:Mucins / Q000235:genetics / Q000378:metabolism; D009367:Neoplasm Staging; D018358:Neuroendocrine Tumors / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D018045:Receptors, Oxytocin / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; C429552:MUC13 protein, human; D008565:Membrane Proteins; D009077:Mucins; C569600:OXTR protein, human; D012333:RNA, Messenger; D018045:Receptors, Oxytocin; D008666:Metalloendopeptidases; C053833:meprin A